1. The role of plasmalemma vesicle-associated protein in pathological breakdown of blood-brain and blood-retinal barriers : potential novel therapeutic target for cerebral edema and diabetic macular edemaEsmeralda K. Bosma, Cornelis J. F. van Noorden, Reinier O. Schlingemann, Ingeborg Klaassen, 2018, review article Abstract: Breakdown of the blood–brain barrier (BBB) or inner blood–retinal barrier (BRB), induced by pathologically elevated levels of vascular endothelial growth factor (VEGF) or other mediators, can lead to vasogenic edema and significant clinical problems such as neuronal morbidity and mortality, or vision loss. Restoration of the barrier function with corticosteroids in the brain, or by blocking VEGF in the eye are currently the predominant treatment options for brain edema and diabetic macular edema, respectively. However, corticosteroids have side effects, and VEGF has important neuroprotective, vascular protective and wound healing functions, implying that long-term anti-VEGF therapy may also induce adverse effects. We postulate that targeting downstream effector proteins of VEGF and other mediators that are directly involved in the regulation of BBB and BRB integrity provide more attractive and safer treatment options for vasogenic cerebral edema and diabetic macular edema. The endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), a protein associated with trans-endothelial transport, emerges as candidate for this approach. PLVAP is expressed in a subset of endothelial cells throughout the body where it forms the diaphragms of caveolae, fenestrae and trans-endothelial channels. However, PLVAP expression in brain and eye barrier endothelia only occurs in pathological conditions associated with a compromised barrier function such as cancer, ischemic stroke and diabetic retinopathy. Here, we discuss the current understanding of PLVAP as a structural component of endothelial cells and regulator of vascular permeability in health and central nervous system disease. Besides providing a perspective on PLVAP identification, structure and function, and the regulatory processes involved, we also explore its potential as a novel therapeutic target for vasogenic cerebral edema and retinal macular edema.
Keywords: plasmalemma vesicle-associated protein, blood-brain barrier, blood-retinal barrier, cerebral edema, diabetic macular edema
Published in DiRROS: 06.08.2024; Views: 34; Downloads: 16
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2. Dynamic susceptibility contrast enhanced (DSC) MRI perfusion and plasma cytokine levels in patients after tonic-clonic seizuresTatjana Filipovič, Katarina Šurlan Popović, Alojz Ihan, David B. Vodušek, 2017, original scientific article Abstract: Background Inflammatory events in brain parenchyma and glial tissue are involved in epileptogenesis. Blood concentration of cytokines is shown to be elevated after tonic-clonic seizures. As a result of inflammation, blood-brain barrier leakage occurs. This can be documented by imaging techniques, such is dynamic susceptibility contrast enhanced (DSC) MRI perfusion. Our aim was to check for postictal brain inflammation by studying DSC MRI perfusion and plasma level of cytokines. We looked for correlations between number and type of introducing seizures, postictal plasma level of cytokines and parameters of DSC MRI perfusion. Furthermore, we looked for correlation of those parameters and course of the disease over one year follow up. Patients and methods We prospectively enrolled 30 patients, 8%24 hours after single or repeated tonic-clonic seizures. Results 25 of them had normal perfusion parameters, while 5 had hyperperfusion. Patients with hyperperfusion were tested again, 3 months later. Two of 5 had hyperperfusion also on control measurements. Number of index seizures negatively correlated with concentration of proinflammatory cytokines IL-10, IFN-[gamma] and TNF-[alpha] in a whole cohort. In patients with hyperperfusion, there were significantly lower concentrations of antiinflammatory cytokine IL-4 and higher concentrations of proinflammatory TNF-[alpha]. Conclusions Long lasting blood- brain barrier disruption may be crucial for epileptogenesis in selected patients.
Keywords: cytokines, blood-brain barrier, tonic-clonic seizures
Published in DiRROS: 03.06.2024; Views: 211; Downloads: 150
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3. A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruptionShirley Sharabi, Bor Kos, David Last, David Guez, Dianne Daniels, Sagi Harnof, Yael Mardor, Damijan Miklavčič, 2016, original scientific article Keywords: electroporation, blood brain barrier, Peleg-Fermi
Published in DiRROS: 09.05.2024; Views: 259; Downloads: 153
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5. Selective inhibition of NLRP3 inflammasome by designed peptide originating from ASCPetra Sušjan, Duško Lainšček, Žiga Strmšek, Vesna Hodnik, Gregor Anderluh, Iva Hafner Bratkovič, 2020, original scientific article Keywords: blood-brain barrier, inflammation, ▫$IL-1beta$▫, peptide inhibitors
Published in DiRROS: 24.03.2022; Views: 840; Downloads: 530
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